Optically active epoxycyclohexane derivative and epoxycyclohexanone derivative, and process for the preparation thereof

ABSTRACT

An optically active epoxycyclohexane derivative represented by the general formula: ##STR1## wherein R represents a 4-oxycarbonyl-1-hydroxy-3-methyl-3(Z)-buten-1-yl or 4-hydroxycarbonyl-3-methyl-1(E),3(Z)-butadien-1-yl group; and R 1  and R 2  each represent a lower alkoxy group or together form a 1,3-dioxolane ring together with the carbon atom to which they are bonded, 
     and an enantiometer thereof. 
     An optically active epoxycyclohexanone derivative represented by the general formula: ##STR2## wherein R 3  represents a hydrogen atom or a lower alkyl, allyl, aralkyl or aryl group, 
     and an enantiomer thereof. 
     Further, the process for preparing these compounds, is also disclosed.

TECHNICAL FIELD

The present invention relates to an optically active epoxycyclohexanederivative represented by the following general formula (I): ##STR3##wherein R represents a 4-oxycarbonyl-1-hydroxy-3-methyl-3(Z)-buten-1-ylor 4-hydroxycarbonyl-3-methyl-1(E),3(Z)-butadien-1-yl group; and R¹ andR² each represent a lower alkoxy group or together form a 1,3-dioxolanering together with the carbon atoms to which R¹ and R² are bonded,

and an enantiomer thereof; an optically active epoxycyclohexanonederivative represented by the general formula (II): ##STR4## wherein R³represents a hydrogen atom or a lower alkyl, allyl, aralkyl or arylgroup, which is derived from an optically active epoxycyclohexanederivative represented by the general formula (I), and an enantiomerthereof; and a process for the preparation of a compound represented bythe above general formula (I) wherein R is a4-hydroxycarbonyl-3-methyl-1(E),3(Z)-butadien-1-yl group.

The optically active epoxycyclohexane derivative (I) and its enantiomerand optically active epoxycyclohexanone derivative (II) and itsenantiomer according to the present invention serve as importantintermediates for the preparation of abscisic acid represented by thefollowing formula (III) which has not been applied to agriculture as yetin spite of its important activity on plant physiology as a planthormone, so that the utilization thereof in the feature is expected, andxanthoxin represented by the following formula (IV) which is moredifficultly available than abscisic acid and therefore has not beenapplied to agricultural production in spite of its activity equivalentto that of abscisic acid, in the form of a natural type optical isomeror an enantiomer thereof: ##STR5##

BACKGROUND ART

Up to this time, several processes for preparing optically activeabscisic acid have been known. These processes are classified into (i) agroup of processes characterized by using an optically active rawmaterial (see K. Mori, Tetrahedron Lett., 1973, 2635; M. Shibasaki, S.Terashima and S. Yamada, Chem. Pharm. Bull., 1976, 24, 315; and K.Kienzle, H. Mayer, R. E. Minder and H. Thommen, Helv. Chim. Acta, 1978,61, 2616), (ii) a group of fermentation processes using a microorganism[see Japanese Patent Laid-Open No. 36393/1983 and the abstracts of the30th Symposium on the Chemistry of Natural Products (Fukuoka, 1988),p.332 ] and (iii) a group of processes comprising preparing racemicabscisic acid which is not optically active and separating the racemicmodification into optically active isomers by optical resolution (see R.S. Burden and H. F. Taylor, Pure & Appl. Chem., 1976, 47, 203).

However, the processes of the group (i) are disadvantageous in that theoptically active raw material is generally difficultly available and thefermentation processes of the group (ii) are unfit for practical useowing to their low productivity. The optical resolution processes of thegroup (iii) have disadvantages due to optical resolution in that theoperation is troublesome and the objective optically active substancecan be obtained only in a low yield even by following a process using anoptically inactive racemic modification of a compound represented by thegeneral formula (VI) or (VII) which will be described below as anintermediate (see M. G. Constantino, P. Losco and E. E. Castellano, J.Org. Chem., 1989, 54, 681), which process is one of the most efficientprocesses among known processes for preparing a racemic modification.

Although optically active abscisic acid is demanded because of itshigher activity as a plant hormone than that of racemic one (see R. S.Burden and H. F. Taylor, Pure & Appl. Chem., 1976, 47, 203), opticallyactive abscisic acid is now much more expensive than racemic one.

On the other hand, not a few processes for preparing xanthoxin have alsobeen known. For example, there have been known a process (i)characterized by using β-ionone as a starting material (see R. S.Burder, G. W. Dawson and H. F. Taylor, Phytochem., 1972 11, 2295 and H.F. Taylor and R. S. Burder, J. Exp. Bot., 1973, 24, 873) and a process(ii) characterized by using isophorone as a starting material (see T.Oritani and K. Yamashita, Agr. Biol. Chem., 1973, 37, 1215). However,the processes (i) and (ii) are ones for preparing optically inactiveracemic xanthoxin, being unimportant. Further, although a process (iii)for preparing optically active xanthoxin from an optically active4-hydroxycyclocitral as a starting material has been also known (see F.Kienzle, H. Mayer, R. E. Minder and H. Thommen, Helv. Chim. Acta, 1978,61, 2616), this process is also disadvantageous in that the opticallyactive starting material is difficultly available.

DISCLOSURE OF INVENTION

The inventors of the present invention have found that an opticallyactive epoxycyclohexane derivative represented by the general formula(I) and an optically active epoxycyclohexanone derivative represented bythe general formula (II) can be efficiently prepared from an easilyavailable asymmetric epoxy aldehyde represented by the general formula(V) which will be described below as a starting material and thatoptically active abscisic acid represented by the formula (III) andoptically active xanthoxin represented by the formula (IV) can beprepared from the above optically active epoxycyclohexane orepoxycyclohexanone derivative in a few steps. The present invention hasbeen accomplished on the basis of these findings.

The epoxycyclohexane derivative represented by the general formula (I)and the epoxycyclohexanone derivative represented by the general formula(II) can be prepared via the following steps 1 to 4.

Further, optically active abscisic acid (III) and optically activexanthoxin (IV) can be easily prepared from the compound represented bythe general formula (I) or (II) via the following steps A to F. ##STR6##wherein R³ represents a hydrogen atom or a lower alkyl, allyl, aralkylor aryl group; R⁴ represents a lower alkyl, allyl, aralkyl or arylgroup; R⁵ and R⁶ each represent a lower alkyl group or together form adioxolane ring together with the carbon atoms to which R⁵ and R⁶ arebonded.

Although the general formulas (Ia), (Ib) and (II) show respectivecompounds each in the form of one optical isomer, the same relationshipcan apply to the enantiomers of the isomers.

The above steps will now be described successively in detail.

Step 1

In this step, an optically active aldehyde represented by the generalformula (V) is reacted with a 3-(halomethyl)-3-methylacrylic ester inthe presence of zinc to give an optically active4,4-dialkoxy-1-(5,6-dihydro-2H-4-methyl-2-oxopyran-6-yl)-1,2-oxo-2,6,6-trimethylcyclohexanerepresented by the general formula (VI) and an optically active4,4-dialkoxy-1-[4-(alkoxycarbonyl)-1-hydroxy-3-methyl-3-buten-1-yl]-1,2-oxo-2,6,6-trimethylcyclohexanerepresented by the general formula (Ia). In the general formula (V), R⁵and R⁶ may be each a methyl, ethyl, n- or i-propyl or n-, i-, sec- ort-butyl group. R⁵ and R⁶ need not always be the same. Further, R⁵ and R⁶may together form a 1,3-dioxa ring together with the carbon atoms towhich they are bonded and it is preferable from the standpoint ofstability and hydrolyzability that the ring be a 1,3-dioxolane ringderivative. On the other hand, in the 3-(halomethyl)-3-methylacrylicester to be used in this step, X may be a chlorine, bromine or iodineatom. Particularly, such an ester wherein X is a bromine atom ispreferable because of its easiness in preparation and its highreactivity. Further, the R⁴ group constituting the ester includes loweralkyl groups such as methyl, ethyl n- and i-propyl and n-, i-, sec- andt-butyl groups; substituted and unsubstituted allyl groups; aralkylgroups such as benzyl, p-methoxybenzyl and p-nitrobenzyl groups; andphenyl and substituted phenyl groups. The3-(bromomethyl)-3-methylacrylic ester which is one of the raw materialto be used in this step is known to be easily preparable by brominatinga 3,3-dimethylacrylic ester (see I. Ahmad, R. N. Gedye and A. Nechvatal,J. Chem. Soc. (C), 1968, 185). Further, the aldehyde represented by thegeneral formula (V) which is the other raw material is also known to beeasily preparable through asymmetric epoxidization in the form of anoptically active substance (see M. Acemoglu, P. Uebelhart, M. Rey and C.H. Eugster, Helv. Chim. Acta, 1988, 71, 931 and the Referential Exampleswhich will be described below).

The condensation is conducted under so-called Reformatsky reactionconditions. In conducting the condensation practically, it is necessaryto use zinc in an amount of 1.0 to 5.0 equivalents, preferably 2.0 to3.0 equivalents. It is suitable that the 3-(bromomethyl)-3-methylacrylicester be used in an amount of 1.2 to 1.5 equivalents. The condensationis preferably conducted in a solvent such as ether, tetrahydrofuran,dioxane, benzene or toluene. The reaction temperature is 0° to 150° C.,preferably 20° to 50° C. The reaction of this step gives a mixturecomprising a lactone compound (VI) which is a cyclization product and anester (Ia), which can be easily separated by a suitable means such ascolumn chromatography.

Step 2

In this step, an optically active acetal represented by the generalformula (VI) is converted into optically active1-(5,6-dihydro-2H-4-methyl-2-oxopyran-6-yl)-1,2-oxo-2,6,6-trimethylcyclohexan-4-onerepresented by the formula (VII) by treatment with an acid. Thistreatment is conducted under mildly acid conditions, wherein a dilutesolution of hydrochloric, sulfuric, phosphoric, camphorsulfonic, ormethanesulfonic acid or an organic acid such as formic, acetic or oxalicacid may be used. The solvent to be used in this step includes water;alcohols such as methanol and ethanol; watersoluble ethers such as THFand dioxane; and mixtures of two or more of them. Alternatively, thetreatment may be conducted in a two-layer or two-phase system comprisingan aqueous acid solution or a silica gel containing an acid adsorbedthereon and a water-incompatible solvent such as methylene chloride,chloroform, benzene or ether. Generally, neither heating nor cooling isparticularly necessary for the treatment.

Step 3

In this step, the optically active lactone or ester represented by thegeneral formula (VI) or (Ia) which has been prepared in the above Step 1is converted into an optically active4,4-dialkoxy-1-[4-(oxycarbonyl)-3-methyl-1,3-butadien-1-yl]-1,2-oxo-2,6,6-trimethylcyclohexanerepresented by the general formula (Ib) by treatment with a base. Thebase to be used in this step includes hydroxides of alkali and alkalineearth metals, such as sodium hydroxide, potassium hydroxide, lithiumhydroxide and barium hydroxide; alkali metal carbonates such as sodiumcarbonate and potassium carbonate; quaternary ammonium hydroxides suchas benzyltrimethylammonium hydroxide; alkali metal alkoxides such assodium methoxide, sodium ethoxide, sodium t-butoxide and potassiumt-butoxide; and ammonia. The solvent to be used in this step includeswater, methanol, ethanol, ether, THF, dioxane, pyridine and mixtures oftwo or more of them.

Step 4

In this step, an optically active diene acetal represented by thegeneral formula (Ib) is converted into1-[4-(oxycarbonyl)-3-methyl-1,3-butadien-1-yl]-1,2-oxo-2,6,6-trimethylcyclohexan-4-onerepresented by the general formula (II) by treatment under mildly acidconditions. The acid to be used in this step includes hydrochloric,sulfuric, phosphoric, camphorsulfonic, methanesulfonic and perchloricacids. In order to avoid the concurrence of Step C, the treatment mustbe conducted either with a dilute acid or at a low temperature. Theobject of avoiding the concurrence of Step C can be easily attained bytreating the acetal (Ib) with 1 to 10% perchloric acid under coolingwith ice.

Optically active abscisic acid can be prepared from the compound (Ib) or(II) thus prepared according to the present invention via Step B or Cwhich will be described below. Further, optically active abscisic acidcan be also prepared from the compound (VII) which has been foundseparately by the inventors of the present invention via the followingStep A.

Step A

In this step, the optically active keto epoxide represented by theformula (VII) is converted into optically active abscisic acidrepresented by the formula (III) by treatment with a base. In this step,the process described in the above Step 3 can be used as such.

The abscisic acid (III) prepared from the intermediate represented bythe formula (VII) exhibits positive optical rotation and has the sameabsolute configuration as that of natural one (see F. Kienzle, Mayer, R.E. Minder and H. Thommen, Helv. Chim. Acta, 1978, 61, 2616).

Step B

In this step, an optically active acetal represented by the generalformula (Ib) is converted into abscisic acid represented by the formula(III) by treatment with an acid.

In conducting this step, the process described in the above Step 2 canbe used as such.

Step C

In this step, an optically active cyclohexanone represented by thegeneral formula (II) is converted into abscisic acid represented by theformula (III) by treatment with an acid. In conducting this step, theprocess described in the above Step B can be used as such.

Further, optically active xanthoxin can be prepared from the compoundrepresented by the general formula (II) via the following Steps D, E andF.

Step D

In this step, the keto group of an epoxycyclohexanone derivativerepresented by the general formula (II) is selectively reduced into ahydroxyl group to give a1-[4-(oxycarbonyl)-3-methyl-1,3-butadien-1-yl]-4-hydroxy-1,2-oxo-2,6,6-trimethylcyclohexanerepresented by the general formula (VIII). Preferable examples of thereducing agent to be used in this step include sodium borohydride,lithium aluminum hydride, diisobutylaluminum hydride, K-SELECTRIDE®, andL-SELECTRIDE®. The reduction is conducted in a solvent suitably selectedfrom among water, methanol, ethanol, ethyl ether, tetrahydrofuran,toluene and mixtures of two or more of them depending upon the reducingagent used.

The substances of the general formula (VIII) which are the products inthis step have already been known and the preparation of opticallyactive xanthoxin therefrom has already been accomplished (see F.Kienzle, H. Mayer, R. E. Minder and H. Thommen, Helv. Chim. Acta, 1978,61, 2616).

Step E

In this step, an epoxycyclohexanol derivative represented by the generalformula (VIII) is further reduced into1-(5-hydroxy-3-methyl-1,3-pentadien-1-yl)-4-hydroxy-1,2-oxo-2,6,6-trimethylcyclohexanerepresented by the formula (IX). The reduction in this step is conductedunder the conventional conditions for reducing a carboxyl or ester groupinto a hydroxymethyl group. For example, lithium aluminum hydride ordiisobutylaluminum hydride is preferably used as a reducing agent in thereduction. The reduction is conducted in a solvent suitably selectedfrom among ethyl ether, tetrahydrofuran, toluene and mixtures of two ormore of them depending upon the reducing agent used.

By treating an epoxycyclohexanone derivative represented by the generalformula (II) with an excess of a reducing agent under the conditionsemployed in this strip, the diol derivative represented by the formula(IX) can be obtained without isolating an intermediate represented bythe general formula (VIII). In other words, the Steps D and E can beconducted at a stroke.

The diol derivative of the formula (IX) which is a product in this stepis a known substance and the preparation of optically active xanthoxintherefrom has already been accomplished (see F. Kienzle, H. Mayer, R. E.Minder and H. Thommen, Helv. Chim. Acta, 1978, 61, 2616).

Step F

In this step, the diol represented by the formula (IX) is converted intooptically active xanthoxin through the selective oxidation of theprimary hydroxyl group into an aldehyde group. The oxidizing agent to beused in the selective oxidation is preferably active manganese dioxide.

The reaction conditions for such selective oxidation have already beenknown and can be applied as such to this step (see F. Kienzle, H. Mayer,R. E. Minder and H. Thommen, Helv. Chim. Acta. 1978, 61, 2616).

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention will now be described in more detail by referringto the following Examples and Referential Examples.

REFERENTIAL EXAMPLE 1 ##STR7##

80 mg of powdery molecular sieves 3A was added to 8 ml of anhydrousmethylene chloride in an argon atmosphere. The obtained mixture wascooled to -20° C., followed by the addition of 39 μl (15 mole %) ofD-(-)-diethyl tartrate (DET) and 43 μl (10 mole %) oftetraisopropoxytitanium. 378 μl (1.63 mmol) of a 2.4M solution oft-butyl hydroperoxide (TBHP) in isooctane was dropped into the mixtureobtained above. After 45 minutes, a solution of 314 mg (1.4 mmol) of4,4-ethylenedioxy-2,6,6-trimethyl-1-cyclohexenemethanol in anhydrousmethylene chloride (0.5 ml) was dropped into the resulting mixture.After 4.5 hours, 900 μl of distilled water and 1.5 ml of a 10% solutionof sodium hydroxide in a saturated aqueous solution of sodium chloridewere added to the resulting mixture successively. After one hour, themethylene chloride layer was recovered and the aqueous layer wasextracted with methylene chloride. The methylene chloride layers werecombined, dehydrated over anhydrous sodium sulfate and distilled in avacuum to remove the solvent. 351 mg of a crude product was obtained.This crude product was purified by silica gel column chromatography(hexane/ethyl acetate=7:1) to give 252 mg (75%) of objective4,4-ethylenedioxy-1,2-oxo-2,6,6-trimethylcyclohexanemethanol. 20 mole %of a shift reagent Eu(tfc)₃ was added to the pure product and theobtained mixture was subjected to H-NMR spectroscopy. The optical yieldwas about 90%.

¹ H-NMR(CDCl₃): δ 1.09(s,3H), 1.17(s,3H), 1.32(dd,1H,J=2.3,13.8),1.41.(s,3H), 1.63(d,1H,J=13.8), 1.87(t.1H,J=5.1),2.00(dd,1H,J=2,3,15.6), 2.25(d,1H,J=15.6), 3.71(dd,1H,J=4.9,11.3),3.77˜3.91(m,4H+1H).

MS: 229(m+1) 213(M--OH).

[α]_(D) ²⁰ :+19.5 (CO.84, CHCl₃).

REFERENTIAL EXAMPLE 2 ##STR8##

140 μl (1.59 mmol, 1.1 equivalents) of oxalyl chloride and 225 μl (3.13mmol, 2.2 equivalents) of anhydrous dimethyl sulfoxide (DMSO) weredissolved in 7 ml of anhydrous methylene chloride in an argonatmosphere. After 10 minutes, a solution of 329 mg (1.442 mmol) of4,4-ethylenedioxy-1,2-oxo-2,6,6-trimethylcyclohexanemethanol in 2 ml ofanhydrous methylene chloride was dropped into the solution preparedabove. After 20 minutes, 1.5 ml (10.8 mmol, 7.5 equivalents) oftriethylamine was added to the resulting mixture. Further, after 10minutes, distilled water was added to the resulting mixture to give ananhydrous methylene chloride layer and an aqueous layer. The methylenechloride layer was recovered and the aqueous layer was extracted withmethylene chloride. The methylene chloride layers were combined,dehydrated over anhydrous sodium sulfate and distilled in a vacuum toremove the solvent. 322 mg (99%) of4,4-ethylenedioxy-1,2-oxo-2,6,6-trimethylcyclohexanecarboxaldehyde wasobtained.

¹ H-NMR(CDCl₃): δ 1.08(s,3H), 1.31(s,3H), 1.32(dd,1H,J=1.9,13.8),1.46(s,3H), 1.71(d,1H,J=13.8), 2.09(dd,1H,J=1.9,15.8),2.30(d,1H,J=15.8), 3.82˜3.90(m,2H), 3.91˜3.95(m,2H), 9.78(s,1H).

EXAMPLE 1 ##STR9##

200 mg (4 equivalents) of powdery zinc activated by the processdescribed in Reagents for Organic Synthesis vol.1, p.1285 and 10 mg ofiodine were put in an argon atmosphere, followed by the addition of 1.5ml of anhydrous THF. The obtained mixture was cooled with ice, followedby the addition of 313 mg (1.58 mmol, 2 equivalents) of methyl3-(bromomethyl)-3-methylacrylate (Z/E=4:5). The obtained mixture wasstirred for 10 minutes, followed by the dropwise addition of a solutionof 178 mg (0.79 mmol) of the aldehyde ([α]_(D) ²⁰ -56.7 (CO.98, CHCl₃))prepared in the Referential Example 2 in 1.5 ml of anhydrous THF. After30 minutes, the disappearance of the raw material was ascertained,followed by the addition of 5 ml of a saturated aqueous solution ofammonium chloride. The obtained mixture was extracted with diethylether. The organic layer was washed with a saturated aqueous solution ofcommon salt, dehydrated over anhydrous sodium sulfate and distilled in avacuum to remove the solvent. 303 mg of a crude product was obtained.This crude product was purified by silica gel column chromatography(hexane/ethyl acetate=6:1) to isolate an isomeric mixture of4,4-ethylenedioxy-1-{4-(methoxycarbonyl)-1-hydroxy-3-methyl-3-buten-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexanein an amount of 51 mg (19%) and two isomers (lactones 1 and 2) of4,4-ethylenedioxy-1-(5,6-dihydro-2H-4-methyl-2-oxopyran-6-yl)-1,2-oxo-2,6,6-trimethylcyclohexanein amounts of 44 mg (18%) and 68 mg (28%), respectively.

methyl ester mixture

¹ H-NMR(CDCl₃): δ 1.08(s,3H), 1.20(s,3H), 1.31(dd,1H,J=2.5,14),1.52(s,3H), 1.60(d,1H,J=14), 1.97(d,1H,J=2.5), 2.19(dd,1H,J=2.5,16),2.28(d,3H,J=1.3), 2.41˜2.51(m,2H), 2.59(s,1H), 3.69(s,3H),3.82˜3.94(m,4H), 4.25(m,1H), 5.80(dd, 1H,J=1.1,2.4).

[α]_(D) ²⁰ :+35.7 (CO.83, CHCl₃).

lactone 1

mp: 157.5˜161° C.

¹ H-NMR(CDCl₃): δ 1.00(s,3H), 1.30(dd,1H, J=2.0,13.7), 1.31(s,3H),1.42(s,3H), 1.67(d,1H,J=13.7), 1.99(dd,1H,J=4.7,19.1), 1.99(s,3H),2.07(dd,1H,J=2.0,15.8), 2.21(d,1H,J=15.8), 2.62(qdd,1H,J=1.2,13.5,19.1), 3.78˜3.96(m,4H), 5.04(dd, 1H,J=4.7,13.5), 5.79(d,1H,J=1.5).

MS: 308(M⁺)197 181 113 112 111 86.

[α]_(D) ²⁰ :+38.1 (CO.62, CHCl₃).

lactone 2

¹ H-NMR(CDCl₃): δ 1.21(s,3H), 1.34(dd,1H, J=1.6,13.7), 1.35(s,3H),1.44(s,3H), 1.69(d, 1H,J=13.7), 2.02(t,3H,J=1.2),2.10(dd,1H,J=1.6,15.7), 2.24(d,1H, J=15.7), 2.36(dd,1H,J=3.7,17.5),2.87(qdd,1H,J=1.2,13.5,17.5), 3.83˜3.93(m,4H), 4.52(dd,1H,J=3.7,13.5),5.81(dd,1H,J=1.4,2.3).

[α]_(D) ²⁰ :-59.7 (Cl.02,CHCl₃).

EXAMPLE 2 ##STR10##

716 mg (2.5 equivalents) of potassium methoxide was dissolved in 30 mlof absolute methanol in an argon atmosphere at 0° C., followed by thedropwise addition of a solution of 765 mg (2.5 mmol) of a mixturecomprising4,4-ethylenedioxy-1-(5,6-dihydro2H-4-methyl-2-oxopyran-6-yl)-1,2-oxo-2,6,6-trimethylcyclohexaneand two isomers of4,4-ethylenedioxy1-{4-(methoxycarbonyl)-1-hydroxy-3-methyl-3-buten1-yl}-1,2-oxo-2,6,6-trimethylcyclohexane(prepared in a similar manner to that of the Example 1) in 10 ml ofabsolute methanol. The obtained mixture was stirred at a roomtemperature for 2 hours to conduct a reaction. In order to acceleratethe reaction, the mixture was heated to 60° C. and stirred for 2 hours.The reaction mixture was neutralized with a saturated aqueous solutionof ammonium chloride, followed by the addition of a small amount of 2Nhydrochloric acid. The obtained mixture was extracted with diethylether. The organic layer was washed with a saturated aqueous solution ofsodium chloride, dehydrated over anhydrous sodium sulfate and distilledin a vacuum to remove the solvent. 688 mg (92%) of4,4-ethylenedioxy-1-{4-(hydroxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexanewas obtained. This product was treated with diazomethane to give amethyl ester quantitatively. carboxylic acid

¹ H-NMR(CDCl₃): δ 1.00(s,3H), 1.21(s,3H), 1.25(s,3H),1.35(dd,1H,J=2.0,13.7), 1.74(d,1H,J=13.7), 2.05(d,1H,J=1.2),2.05(dd,1H,J=2.0,15.7), 2.28(d,1H,J=15.7), 3.82˜3.96(m,4H),5.72(d,1H,J=1.1), 6.34(dd,1H,J=0.5,16.0), 7.63(dd,1H, J=0.7,16.0).

[α]_(D) ²⁰ : +19.9 (Cl.01, CHCl₃).

methyl ester

¹ H-NMR(CDCl₃): δ 1.00(s,3H), 1.22(s,3H), 1.25(s,3H)1.34(dd,1H,J=2.2,14), 1.74(d,1H,J=14), 2.01(s,3H), 2.04(dd,1H,J=2.2,16), 2.28(d,1H,J=16), 3.70(s,3H), 3.82˜3.95(m,4H),5.70(brs,1H), 6.28(d, 1H,J=16), 7.62(d,1H,J=16).

EXAMPLE 3 ##STR11##

11 mg (0.036 mmol) of4,4-ethylenedioxy-1-{4-(hydroxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexanewas dissolved in 100 μl of a 10% solution of perchloric acid in a THF/H₂O (1:1) mixture at 4° C. The obtained solution was stirred for 2 hoursand neutralized with a saturated aqueous solution of sodiumhydrogencarbonate. The resulting mixture was extracted with methylenechloride. The organic layer was washed with water, dehydrated overanhydrous sodium sulfate and distilled in a vacuum to remove thesolvent. 8.7 mg (92%) of1-{4-(hydroxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexan-4-onewas obtained.

¹ H-NMR(CDCl₃): δ 1.08(s,3H), 1.16(s,3H), 1.27(s,3H), 1.98(d,1H,J=15),2.20(d,3H, J=5.3), 2.60(dd,1H,J=1.1,20), 2.63(d,1H, J=15),2.87(d,1H,J=20), 5.78(brs,1H), 6.32(d,1H,J=16), 7.72(d,1H,J=16).

IR(KBr disk): 3450, 2980, 1718, 1676, 1246 cm⁻¹.

[α]_(D) ²⁰ :+115.8(CO.81, CHCl₃).

EXAMPLE 4 ##STR12##

74 mg (0.23 mmol) of4,4-ethylenedioxy-1-{4-(methoxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexanewas dissolved in 460 μl, of a 3% solution of perchloric acid in a THF/H₂O (1:1) mixture at 4° C. The obtained solution was stirred for 2 hours,neutralized with a saturated aqueous solution of sodiumhydrogen-carbonate and extracted with methylene chloride. The organiclayer was washed with water, dehydrated over anhydrous sodium sulfateand distilled in a vacuum to remove the solvent. 55 mg (86%) of1-{4-(methoxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexan-4-onewas obtained.

¹ H-NMR(CDCl₃): δ 1.07(s,3H), 1.15(s,3H), 1.27(s,3H), 1.97(d,1H,J=16),2.04(d,3H, J=1.2), 2.59(d,1H,J=20), 2.63(d,1H,J=16), 2.86(d,1H,J=20),3.71(s,3H), 5.75(brs,1H), 6.26(dd,1H,J=0.6,16), 7.74(dd,1H,J=0.7,16).

REFERENTIAL EXAMPLE 3 ##STR13##

1.2 ml of a 10% solution of sodium hydroxide in an ethanol/pyridine(1:1) mixture was cooled with ice, followed by the addition of asolution of1-(5,6-dihydro-2H-4-methyl-2-oxopyran-6-yl)-1,2-oxo-2,6,6-trimethylcyclohexan-4-onein 0.25 ml of pyridine. After 2 hours, the disappearance of the rawmaterial was ascertained. The reaction mixture was diluted with diethylether and the pH thereof was adjusted to about 2 with 1M hydrochloricacid. The resulting mixture was extracted with diethyl ether. Theorganic layer was washed with a saturated aqueous solution of sodiumchloride, dehydrated over anhydrous sodium sulfate and distilled in avacuum to remove the solvent. 14 mg of a crude product was obtained.This crude product was purified by silica gel column chromatography(hexane/ethyl acetate=4:1) to give 5.3 mg (38%) of (+)-abscisic acid.

¹ H-NMR(CDCl₃): δ 1.03(s,3H), 1.12(s,3H), 1.93(d,3H,J=1.3),2.05(d,3H,J=1.1), 2.30(d,1H,J=17), 2.49(d,1H,J=17), 5.78(brs,1H),5.97(brs,1H), 6.18(d,1H, J=16), 7.81(d,1H,J=16).

[α]_(D) ²⁰ : +383.7(Cl.02, EtOH).

REFERENTIAL EXAMPLE 4 ##STR14##

8.7 mg of4-{4-(hydroxycarbonyl)-3-methyl-1,3-butadien-1-yl}-3,4-oxo-3,5,5-trimethylcyclohexan-1-onewas dissolved in 2 ml of methanol, followed by the addition of 500 μl of1N hydrochloric acid. The obtained mixture was stirred at roomtemperature for one hour, followed by the addition of a saturatedaqueous solution of common salt. The obtained mixture was extracted withmethylene chloride. The organic layer was washed with a small amount ofa saturated aqueous solution of common salt, dehydrated over anhydroussodium sulfate and distilled in a vacuum to remove the solvent. Theresidue was purified by silica gel column chromatography (hexane/ethylacetate=4:1) to give 7.5 mg (87%) of objective (+)-abscisic acid.

¹ H-NMR(CDCl₃): δ 1.03(s,3H), 1.12(s,3H), 1.93(d,3H,J=1.3),2.05(d,3H,J=1.1), 2.30(d,1H,J=17), 2.49(d,1H,J=17), 5.78(brs,1H),5.97(brs,1H), 6.18(d,1H, J=16), 7.81(d,1H,J=16).

[α]_(D) ²⁰ : +383.7(Cl.02, EtOH).

REFERENTIAL EXAMPLE 5 ##STR15##

525 mg (1.703 mmol) of4,4-ethylenedioxy-1-{4-(hydroxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexanewas dissolved in 16 ml of absolute methanol, followed by the addition of3.6 ml of 1N hydrochloric acid. The obtained mixture was stirred at roomtemperature for 19 hours, followed by the addition of a saturatedaqueous solution of common salt. The obtained mixture was extracted withmethylene chloride. The organic layer was washed with a small amount ofa saturated aqueous solution of common salt, dehydrated over anhydroussodium sulfate and distilled in a vacuum to remove the solvent. Theobtained crude product was recrystallized from a hexane/chloroformmixture to give 372 mg (83%) of (+)-abscisic acid.

REFERENTIAL EXAMPLE 6 ##STR16##

12 mg (1.6 equivalents) of lithium aluminum hydride was dissolved in 2ml of anhydrous tetrahydrofuran in an argon atmosphere at 0° C.,followed by the dropwise addition of a solution of 55 mg (0.198 mmol) of1-{4-(methoxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexan-4-onein 0.5 ml of anhydrous tetrahydrofuran. The obtained mixture was stirredfor one hour. A saturated aqueous solution of ammonium chloride wasadded to the resulting mixture to neutralize excess reagent. Theresulting mixture was extracted with diethyl ether. The organic layerwas washed with a saturated aqueous solution of common salt, dehydratedover anhydrous sodium sulfate and distilled in a vacuum to remove thesolvent. 52 mg (94%) of an objective mixture comprising twostereoisomers of4-hydroxy-1-{4-(methoxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexanewas obtained. The isomer ratio was about 1:1.

4β-hydroxyl isomer

¹ H-NMR(CDCl.sub.): δ 1.01(s,3H), 1.15(s,3H), 1.22(s,3H),1.60˜1.66(m,1H), 2.01(d,3H, J=1.2), 2.38(ddd,1H,J=1.7,5.0,14), 3.70(s,H), 3.59˜3.64(m,1H), 5.70(brs,1H), 6.27(d,1H,J=16), 7.60(d,1H,J=16).

4α-hydroxyl isomer

¹ H-NMR(CDCl₃): δ 1.04(s,3H), 1.16(s,3H), 1.22(s,3H),1.36(ddd,1H,J=1.5,3.9,13), 1.90(dd,1H,J=8.4,15), 2.01(s,3H),2.20(ddd,1H,J=1.3,6.7,15), 3.70(s,3H), 3.72˜3.77(m,1H), 5.71(brs,1H),6.20(d,1H,J=16), 7.62(d,1H,J=16).

REFERENTIAL EXAMPLE 7 ##STR17##

60 mg (0.216 mmol) of1-{4-(methoxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexan-4-onewas dissolved in 570 μl of anhydrous tetrahydrofuran in an argonatmosphere at -78° C., followed by the dropwise addition of 432 μl (1equivalent) of a 0.5M solution of K-SELECTRIDE® in tetrahydrofuran. Theobtained mixture was stirred for 30 minutes, neutralized with asaturated aqueous solution of ammonium chloride and extracted withdiethyl ether. The organic layer was washed with a saturated aqueoussolution of common salt, dehydrated over anhydrous sodium sulfate anddistilled in a vacuum to remove the solvent. The residue was purified bysilica gel column chromatography (hexane/ethyl acetate=4:1) to give 23mg (38%) of4β-hydroxy-1-{4-(methoxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexane and 7 mg (12%) of4α-hydroxy-1-{4-(methoxycarbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo-2,6,6-trimethylcyclohexane.

REFERENTIAL EXAMPLE 8 ##STR18##

52 mg (0.186 mmol) of4-hydroxy-1-{4-(methoxy-carbonyl)-3-methyl-1,3-butadien-1-yl}-1,2-oxo2,6,6-trimethylcyclohexane(4α-hydroxyl isomer/4β-hydroxyl isomer=1:1) was dissolved in 5 ml ofanhydrous toluene in an argon atmosphere at -78° C., followed by thedropwise addition of 930 μl (5 equivalents) of a 1.0M solution ofdiisobutylaluminum hydride in hexane. After the obtained mixture hadbeen reacted for one hour, methanol was added to the reaction mixture toneutralize excess reagent, followed by the addition of a saturatedaqueous solution of ammonium chloride. The obtained mixture wasextracted with diethyl ether. The organic layer was washed with asaturated aqueous solution of common salt, dehydrated over anhydroussodium sulfate and distilled in a vacuum to remove the solvent. Theresidue was purified by silica gel column chromatography (hexane/ethylacetate=4:1) to give 21 mg (48%) of4-hydroxy-1-(5-hydroxy-3-methyl-1,3-pentadien-1-yl)-1,2-oxo-2,6,6-trimethylcyclohexaneand 19 mg (44%) of its isomer.

α-diol isomer

¹ H-NMR(CDCl₃): δ 1.01(s,3H), 1.15(s,3H), 1.19(s,3H),1.36(ddd,1H,J=1.4,3.9,13), 1.89(dd,1H,J=8.5,15), 1.87(brs,3H),2.20(ddd,1H,J=1.4,6.7,15), 3.84˜3.91 (m,1H), 4.31(d,2H,J=6.9),5.58(t,1H, J=6.9), 5.90(d,1H,J=16), 6.57(dd,1H, J=0.6,16).

β-diol isomer

¹ H-NMR(CDCl₃): δ 0.98(s,3H), 1.14(s,3H), 1.19(s,3H), 1.24˜1.27(m,2H),1.60˜1.66(m,1H), 1.87(d,3H,J=1.0), 2.38(ddd, 1H,J=1.8,5.1,14),3.87,˜3.94(m,1H), 4.29˜4.34(m,2H), 5.57(t,1H,J=6.8), 5.96(d,1H,J=16),6.56(dd,1H,J=0.6,16).

REFERENTIAL EXAMPLE 9 ##STR19##

7 mg (0.024 mmol) of4β-hydroxy-1-(5-hydroxy-3-methyl-1,3-pentadien-1-yl)-1,2-oxo-2,6,6-trimethylcyclohexanewas mixed with 1 ml of anhydrous methylene chloride and 42 mg (20equivalents) of manganese dioxide in an argon atmosphere. The obtainedmixture was stirred at a room temperature for 2 hours and filtered toremove excess manganese dioxide. The filtrate was distilled in a vacuumto remove the solvent. 5 mg (83%) of xanthoxin was obtained. The α-diolisomer was also treated in a similar manner to that described above togive epixanthoxin.

(-)-xanthoxin

¹ H-NMR(CDCl₃): δ 1.00(s,3H), 1.19(s,3H), 1.21(s,3H), 2.12(brs,3H),3.87˜3.96 (m,1H), 5.88(d,1H,J=8.2), 6.38(d,1H,J=15), 7.21(d,1H,J=15),10.20(d,1H,J=8.2).

epixanthoxin

¹ H-NMR(CDCl₃): δ 1.03(s,3H), 1.20(s,3H), 1.21(s,3H), 2.12(brs,3H),3.86˜3.95 (m,1H), 5.89(d,1H,J=8.1), 6.39(d,1H, J=15), 7.21(d,1H,J=15),10.18(d,1H, J=8.2).

We claim:
 1. An optically active epoxycyclohexanone represented by theformula: ##STR20## and an enantiomer thereof produced by the processcomprising the steps of a) reacting an optically active aldehydederivative represented by the general formula (1): ##STR21## wherein R¹and R² each represent a lower alkoxy group or together form a1,3-dioxolane ring together with the carbon atom to which they arebonded, with a 3-methylcrotonic ester represented by the general formula(2): ##STR22## wherein R⁴ represents a lower alkyl, allyl, aralkyl oraryl group; and X represents a chlorine, bromine or iodine atom, toproduce an optically active epoxycyclohexane having an ester grouprepresented by the general formula (3): ##STR23## wherein R¹, R² and R⁴are the same as described above, b) treating the compound (3) with asolution of alkali metal alkoxide in solvent to produce an opticallyactive epoxycyclohexane having a carboxyl group represented by thegeneral formula (4): ##STR24## wherein R¹ and R² are the same asdescribed above, and c) treating the compound (4) with perchloric acidunder cooling to produce the objective epoxycyclohexanone.